ArticleProceedings of the National Academy of Sciences of the United States of America2008
A gamma-secretase inhibitor and quinacrine reduce prions and prevent dendritic degeneration in murine brains.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 43 citations in OpenAlex.
- Combination of Styrylbenzoazole Compound and Hydroxypropyl Methylcellulose Enhances Therapeutic Effect in Prion-Infected Mice.Molecular neurobiology · 2024Article
- Vectored Immunotherapeutics for Infectious Diseases: Can rAAVs Be The Game Changers for Fighting Transmissible Pathogens?Frontiers in immunology · 2021Review
- Epigenetic Control of the Notch and Eph Signaling Pathways by the Prion Protein: Implications for Prion Diseases.Molecular neurobiology · 2019Article
- Article
- Developing Therapeutics for PrP Prion Diseases.Cold Spring Harbor perspectives in medicine · 2017Review
- Cellular Prion Protein Mediates Pancreatic Cancer Cell Survival and Invasion through Association with and Enhanced Signaling of Notch1.The American journal of pathology · 2016Article
- Brain Aggregates: An Effective In Vitro Cell Culture System Modeling Neurodegenerative Diseases.Journal of neuropathology and experimental neurology · 2016Article
- White matter involvement in sporadic Creutzfeldt-Jakob disease.Brain : a journal of neurology · 2014Article
- Quinacrine promotes replication and conformational mutation of chronic wasting disease prions.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Article
- The DNA virus white spot syndrome virus uses an internal ribosome entry site for translation of the highly expressed nonstructural protein ICP35.Journal of virology · 2013Article
- Therapies for human prion diseases.American journal of neurodegenerative disease · 2013Review
- Therapeutic activity of inhibition of the soluble epoxide hydrolase in a mouse model of scrapie.Life sciences · 2013Article
- Levels of the Mahogunin Ring Finger 1 E3 ubiquitin ligase do not influence prion disease.PloS one · 2013Article
- Granzyme B-induced neurotoxicity is mediated via activation of PAR-1 receptor and Kv1.3 channel.PloS one · 2012Article
- Pharmacokinetics of quinacrine efflux from mouse brain via the P-glycoprotein efflux transporter.PloS one · 2012Article
- Not(ch) just development: Notch signalling in the adult brain.Nature reviews. Neuroscience · 2011Review
- Targets for AD treatment: conflicting messages from γ-secretase inhibitors.Journal of neurochemistry · 2011Article
- Cellular and molecular actions of Methylene Blue in the nervous system.Medicinal research reviews · 2011Review
- The intricate mechanisms of neurodegeneration in prion diseases.Trends in molecular medicine · 2011Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
In prion-infected mice, both the Notch-1 intracellular domain transcription factor (NICD) and the disease-causing prion protein (PrP(Sc)) increase in the brain preceding dendritic atrophy and loss. Because the drug LY411575 inhibits the gamma-secretase-catalyzed cleavage of Notch-1 that produces NICD, we asked whether this gamma-secretase inhibitor (GSI) might prevent dendritic degeneration in mice with scrapie. At 50 d postinoculation with Rocky Mountain Laboratory (RML) prions, mice were given GSI orally for 43-60 d. Because we did not expect GSI to produce a reduction of PrP(Sc) levels in brain, we added quinacrine (Qa) to the treatment regimen. Qa inhibits PrP(Sc) formation in cultured cells. The combination of GSI and Qa reduced PrP(Sc) by approximately 95% in the neocortex and hippocampus but only approximately 50% in the thalamus at the site of prion inoculation. The GSI plus Qa combination prevented dendritic atrophy and loss, but GSI alone did not. Even though GSI reduced NICD levels to a greater extent than GSI plus Qa, it was unable to prevent dendritic degeneration. Whether a balance between NICD and dendrite growth-stimulating factors was achieved with GSI plus Qa but not GSI alone remains to be determined. Although the combination of GSI and Qa diminished PrP(Sc) in the brains of RML-infected mice, GSI toxicity prevented us from being able to assess the effect the GSI plus Qa combination on incubation times. Whether less toxic GSIs can be used in place of LY411575 to prolong survival remains to be determined.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.